There is a perception that phentermine pharmacotherapy for obesity increases blood pressure and heart rate (HR), exposing treated patients to increased cardiovascular risk. We collected data from phentermine-treated (PT) and phentermine-untreated (P0) patients at a private weight management practice, to examine blood pressure, HR, and weight changes. Records of 300 sequential returning patients were selected who had been treated with a low-carbohydrate ketogenic diet if their records included complete weight, blood pressure, and HR data from seven office examinations during the first 12 weeks of therapy. The mean time in therapy, time range, and mode was 92 (97.0), 12–624, and 52 weeks. 14% were normotensive, 52% were prehypertensive, and 34% were hypertensive at their first visit or had a previous diagnosis of hypertension. PT subjects systolic blood pressure/diastolic blood pressure (SBP/DBP) declined from baseline at all data points (SBP/DBP −6.9/−5.0 mm Hg at 26, and −7.3/−5.4 at 52 weeks). P0 subjects' declines of SBP/DBP at both 26 and 52 weeks were −8.9/−6.3 but the difference from the treated cohort was not significant. HR changes in treated/untreated subjects at weeks 26 (−0.9/−3.5) and 52 (+1.2/−3.6) were not significant. Weight loss was significantly greater in the PT cohort for week 1 through 104 (P = 0.0144). These data suggest phentermine treatment for obesity does not result in increased SBP, DBP, or HR, and that weight loss assisted with phentermine treatment is associated with favorable shifts in categorical blood pressure and retardation of progression to hypertension in obese patients.