Our purpose was to examine self-efficacy of knee function, physical activity (PA) and health-related quality of life (HRQoL) in post-meniscectomy patients and controls as well as to explore the impact of gender and the association between outcomes. Ninety-nine post-meniscectomy patients (27% women), mean age 44.5 years, mean (range) of follow-up time 3 (1–5) years, and 94 controls (34% women), mean age 45 years, completed the following questionnaires: the Knee Self-Efficacy Scale (K-SESABC), the Physical Activity Scale (PAS) and the Short Form-36 (SF-36). Patients scored lower than controls in K-SESABC and in the SF-36 subscales Physical Functioning and Bodily Pain (P≤0.002). Forty-six percent of the patients had resumed pre-injury PA, but current PA did not differ between the groups. In the patients, K-SESABC correlated strongly with four physical SF-36 subscales and one mental scale (Vitality) (rs=0.56–0.85, P<0.001) and moderately with three subscales: (rs=0.35–0.46, P<0.001) and with PAS (rs=0.42, P<0.001). Females scored lower than males in K-SESABC (P=0.006) and in four SF-36 subscales (P<0.04), but reported similar PA as men. We conclude that meniscectomy in middle-aged individuals may lead to lower self-efficacy of knee function, a sedentary lifestyle and poorer HRQoL.